Repetitive hyperbaric oxygen exposures enhance sensitivity to convulsion by upregulation of eNOS and nNOS

Background: Repetitive hyperbaric oxygen (HBO) exposures as preconditioning methods produce ischemic tolerance, but may increase the risk of convulsions in patients. The purpose of this study was to investigate the mechanisms in increased sensitivity to convulsions and the role of nitric oxide (NO) and its synthases after repetitive HBO exposures. Methods: Mice were randomly assigned into three groups: HBO group, hyperbaric air (HBA) group and normobaric air (NBA) group. Mice in HBO or HBA group were exposed to hyperbaric oxygen or hyperbaric air respectively for 60 min twice daily for 3 consecutive days (2.5 atmosphere absolute [ATA]). 24 h after the last exposure, mice were exposed to HBO (100% O-2, 6 ATA). The latency of convulsions was recorded. In addition, the levels of NO, NADPH-diaphorase, mRNA and protein expressions of NOS isofonns in hypothalamus and hippocampus were determined. Results: Latency to seizures was significantly shortened in mice after six HBO pre-exposures. The level of NO in hypothalamus in HBO group was increased. The number of NADPH-d positive cells and the levels of protein and mRNA of eNOS and nNOS in hypothalamus and hippocampus were increased. Conclusion: After repeated HBO exposures, elevated NO may enhance the sensitivity to convulsions and this may lead to seizures during the subsequent oxygen exposures. Prevention of seizures is needed when HBO is used as preconditioning method. (C) 2008 Elsevier B.V. All rights reserved.